title: In vivo distribution and antitumor activity of doxorubicin-loaded N-isopropylacrylamide-co-methacrylic acid coated mesoporous silica nanoparticles and safety evaluation.
abstract: The objective of this study was to develop and evaluate the antitumor activity and the safety of a delivery system containing mesoporous silica nanoparticles (MSN) coated with pH-responsive poly (N-isopropylacrylamide-co-methacrylic acid; P NIPAM-co-MAA) for doxorubicin (DOX) delivery (P-MSN-DOX) in vitro and in vivo. We reported that P-MSN-DOX nanoparticles (190 ± 30 nm) offered a DOX-loading coefficient of more than 20%. DOX release from the P-MSN-DOX formulation was pH-dependent with enhanced antitumor effects in vitro compared with traditional MSN-DOX, which was weakly cytotoxic due to negligible drug release at tested pHs. P-MSN-DOX circulated longer, with less cardiac and renal accumulation as shown by pharmacokinetics and biodistribution studies in vivo. Also, the P-MSN-DOX delivery system had greater antitumor activity in mice bearing a murine sarcoma S-180 cell line. This finding was correlated with both in vitro and in vivo. Subacute toxicity tests revealed a low P-MSN-DOX toxicity in vivo, as well. Thus, P-MSN-DOX appears to be an efficacious and safe cancer treatment strategy.
authors.affiliation: Key Laboratory of Smart Drug Delivery (Fudan University), Ministry of Education, Department of Pharmaceutics, School of Pharmacy, Fudan University, Shanghai, China.
authors.forename: Yanzuo
authors.initials: Y
authors.lastname: Chen
authors.forename: Wuli
authors.initials: W
authors.lastname: Yang
authors.forename: Baisong
authors.initials: B
authors.lastname: Chang
authors.forename: Hangting
authors.initials: H
authors.lastname: Hu
authors.forename: Xiaoling
authors.initials: X
authors.lastname: Fang
authors.forename: Xianyi
authors.initials: X
authors.lastname: Sha
mesh_terms: D000178:Acrylamides / Q000737:chemistry*; D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology; D004317:Doxorubicin / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000494:pharmacology; D004337:Drug Carriers / Q000737:chemistry; D016503:Drug Delivery Systems; D006863:Hydrogen-Ion Concentration; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D053758:Nanoparticles; D011109:Polymethacrylic Acids / Q000737:chemistry*; D016062:Porosity; D051381:Rats; D017207:Rats, Sprague-Dawley; D012510:Sarcoma 180 / Q000188:drug therapy / Q000473:pathology; D012822:Silicon Dioxide / Q000737:chemistry; D014018:Tissue Distribution; D059551:Toxicity Tests, Subacute
chemical_list: D000178:Acrylamides; D000903:Antibiotics, Antineoplastic; D004337:Drug Carriers; D011109:Polymethacrylic Acids; C085085:poly(N-isopropylacrylamide-co-methacrylic acid); D012822:Silicon Dioxide; D004317:Doxorubicin
keywords: 3-(4,5-dimethyl-thiazol-2-yl)-2,5-diphenyl-tetrazolium bromide; AST; AUC; Antitumor activity; CK; CL; DL%; DOX; DOX-loaded MSN; DOX-loaded P-MSN; Doxil; Doxorubicin; EPR; ER%; MRT; MSN; MSN-DOX; MTT; Mesoporous silica nanoparticles; N-isopropylacrylamide-co-methacrylic acid; Nanoparticles; P (NIPAM-co-MAA); P (NIPAM-co-MAA) coated MSN; P-MSN; P-MSN-DOX; PEG-liposome of DOX; RBC; RES; Safety evaluation; V(d); VPTT; WBC; apparent volume of distribution; area under the plasma concentration-time curve; aspartate transaminase; clearance; creatine kinase; doxorubicin; drug-loading coefficient; elimination half-life; encapsulation ratio; enhanced permeability and retention; mean residence time; mesoporous silica nanoparticles; poly (N-isopropylacrylamide-co-methacrylic acid); red blood cell; reticulo-endothelial system; t(1/2)(β); volume phase transition temperature; white blood cell